Density dependence of maximal expiratory air flow in asthmatics with exacerbation of their disease

In an effort to evaluate the relationship between the site of air-flow obstruction and rate of improvement with therapy, we studied 20 asthmatics with spirometry, before and after bronchodilator, using air and 80% helium-20% oxygen (He-O2). Studies were obtained on 3 consecutive days after hospital admission and approximately 18 days after discharge. Greater He-O2 response ([Vmax50(He-O2)--Vmax50(air)]/predicted Vmax50) X 100, was associated with: less cigarette consumption (p less than 0.02), lesser frequency of chronic productive cough (p less than 0.02), more symptom-free intervals (p less than 0.02), and greater frequency of allergic rhinitis (p less than 0.03). Patients with greater He-O2 response (Group 1) reached maximal improvement in air flow by Hospital Day 2, whereas those with a lesser He-O2 response (Group 2) continued to improve throughout the observation period. The Group 1 mean peak expiratory flow rate (PEFR) improved by 24% of predicted per day to maximum, which was significantly greater (p less than 0.025) than the 11% per day rate of improvement of Group 2. The He-O2 response remained relatively stable throughout the course of the study except for 3 patients who dramatically improved their response with therapy. A highly significant correlation, adjusted for regression to the mean, (r = 0.95, p less than 0.0001) was found between mean baseline percent predicted Vmax50 and the mean He-O2 response. After adjustment for regression to the mean, there was no significant relationship between the degree of prebronchodilator He-O2 response and increase in He-O2 response with bronchodilator.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monoclonal antibodies and magnetic microspheres for the depletion of leukaemic cells from bone marrow harvested for autologous transplantation

The use of a panel of monoclonal antibodies and anti-mouse immunoglobulin-coated microspheres is described for the depletion of leukaemic blasts from bone marrow. Marrow treated in this way rapidly reconstitutes haemopoietic function after high-dose consolidation chemoradiotherapy. The recovery of cells from bone marrow is similar but not identical to results obtained on removal of neuroblasts from marrow to be used for autologous transplant. This is probably a reflection of the cross-reactivity of 'anti-leukaemic' antibodies with a variety of haemopoietic progenitor cells. The study described here demonstrates the feasibility of using this method to purge leukaemic cells from bone marrow. A much larger randomised study between patients receiving either purged or non-purged bone marrow would be necessary to validate the need to remove small numbers of tumour cells from bone marrow.     

Surgical management of major pancreatic injury in children.

INTRODUCTION: Major or complicated pancreatic trauma in children is uncommon and management strategies remain controversial. The aim of this study was to evaluate our experience with both early and delayed surgery in these pediatric cases. METHODS: We carried out a retrospective analysis of data of pediatric patients with major or complicated pancreatic injury operated on between January 1994 and December 2005 in our pediatric trauma center. RESULTS: Thirteen children (9 boys and 4 girls) with a mean age of 8.5 years (range 3 - 16 years) were operated for major or complicated pancreatic injury. The extent of injury was: grade II (major contusion without duct injury or tissue loss) in 4 children; grade III (distal transection) in 5 children and grade IV injury (proximal transection) in four patients. Pseudocyst developed in 8 children: 4 with grade II injury, 2 with grade III injury and 2 with grade IV injury (one with abdominal pseudocyst and one with an abdominal and a mediastinal pseudocyst). Early diagnosis and operation was achieved in 5 cases, while delayed diagnosis and operation occurred in 8. Three children underwent cystogastrostomy; 6 had a spleen-sparing distal pancreatectomy and 4 had resection with Roux-en-Y jejunostomy drainage. Endoscopic retrograde cholangiopancreaticography (ERCP) was the most useful diagnostic tool in assessing ductal injury. There were no deaths or long-term morbidity in our group of patients. CONCLUSIONS: Our results support the view that early operation is important in ductal pancreatic injury. We recommend transferring children with a suspected ductal injury to a tertiary center with experience in both pediatric ERCP and pancreatic surgery.     

Effects of residence and race on burden of travel for care: cross sectional analysis of the 2001 US National Household Travel Survey

Background  

Travel burden is a key element in conceptualizing geographic access to health care. Prior research has shown that both rural and minority populations bear disproportionate travel burdens. However, many studies are limited to specific types of patient or specific locales. The purpose of our study was to quantify geographic and race-based differences in distance traveled and time spent in travel for medical/dental care using representative national data.     

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Characterization of cell death events induced by anti-neoplastic drugs cisplatin, paclitaxel and 5-fluorouracil on human hepatoma cell lines: Possible mechanisms of cell resistance.

Two different hepatoma cell lines were incubated for 48h with chemotherapeutic drugs cisplatin, paclitaxel and 5-FU to determine their ability to induce cytotoxicity and DNA fragmentation as well as to modify the expression of some cell death-related genes that could be involved in the resistance to therapy. We observed that cisplatin and paclitaxel induced cytotoxicity, but significant differences between both cell lines, were found only in the case of paclitaxel. At 48h, apoptosis was clearly present in Hep3B cells treated with cisplatin and HepG2 cells treated with paclitaxel. 5-FU induced cytotoxicity in both cell lines but only at higher concentrations than the other two drugs, triggering apoptosis and necrosis in HepG2 cells and only necrosis in Hep3B. When a time course was performed for the first 8h of treatment to elucidate the initial mechanism of cell death responsible for DNA fragmentation, we observed that 5-FU in Hep3B, and cisplatin in both cell lines, induces primary necrosis, whereas at the concentration tested here, paclitaxel clearly triggers apoptosis in both cell lines. HepG2 cells were weakly sensitive to 5-FU in the first 8h of treatment, so the primary mechanism of cell death was not clear, but results seem to indicate that it could be apoptosis. At 48h, Bax was not up-regulated with any of the treatments, whereas cisplatin was able to induce Bcl-xL down-regulation in both cell lines. Treatment with 5-FU also down-regulated Bcl-xL in HepG2 cells. We also measured variations in the expression of survivin, an inhibitor of apoptosis that has also been involved in mitototic catastrophe. Hep3B cells seem to show an increase in protein levels with all treatments. Exposure to paclitaxel resulted in the highest effect. In the case of HepG2 cells, there was a decrease in survivin expression when cells were treated with 5FU and paclitaxel, both treatments showing complete loss of the protein. Using an antibody that recognizes unprocessed caspase-3, we observed that the enzyme was assumingly activated in HepG2 cells treated with 5FU and paclitaxel, but only weakly after treatment with cisplatin. Hep3B cells did not show activation since the levels of the pro-enzyme remained the same as that in the control. In conclusion, the three drugs tested in this study could induce cell death, with paclitaxel being more effective inducing apoptosis. 5FU was only effective at high doses and its mechanism seems to be primarily related to necrosis in Hep3B and probably apoptosis in HepG2. Cisplatin mechanism of cell death is probably mediated by the decrease in anti-apoptotic protein Bcl-xL whereas paclitaxel and 5FU are decreasing the apoptosis inhibitor survivin. According to pro-enzyme levels, caspase-3 was only activated in HepG2 cells, whereas in the case of Hep3B cells the mechanisms of toxicity appear to be caspase-3-independent at the time and concentrations tested in this study. The resistance of Hep3B cells to death induced by chemotherapy could be related to an increase in the expression of IAP survivin, which can decrease cell response to the treatment or even switch the type of death from apoptosis to another kind, making therapy less efficient.